ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Zhi Li,Tao Guo,Yuehua Hu,Yuan Qiu,Yang Liu,Huimeng Wang,Yi Li,Xian Chen,Jibin Song,Huanghao Yang
Even though black phosphorus (BP) has exhibited outstanding capabilities in biomedical, physical, and energy fields, the issues of degradation under ambient conditions and unreactive functional interface limit its further application. There are numerous methodologies utilized to prevent BP degradation; however, these methods usually generate further problems and normally do not involve alterations to the chemically inert BP. Herein, for the first time, we propose a simple and efficient strategy to prepare and modify BP nanosheets (p-BPNSs) by employing aromatic 1-pyrenylbutyric acid through a noncovalent π–π stacking interaction. This strategy not only adopts a novel strategy for enhancing the stability of BPNSs but also paves a convenient way to anchor other active biomolecules such as a targeting effect to extend the biomedical applications of BPNSs. The modified p-BPNSs exhibit enhanced physical and chemical stabilities as well as rich carboxyl groups for further modification. In this work, RGD-modified p-BPNSs exhibit targeted photothermal therapy ability against cancer in both in vitro and in vivo studies, owing to anchoring of arginine-glycine-aspartic acid (RGD) tripeptides, which could target nanosheets into the tumor site through systematic circulation. Consequently, this work not only provides a new concept for modifying and protecting the BP but also opens a novel window for extending the biomedical application of BP by surface engineering.
研究领域:
材料科学
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纳米技术
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生物医学工程
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癌症研究
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DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 39
·
IF 12.5
Taige Chen,Rui Liu,Qin Chen,Xuebing Feng,Bin Kong,Yuanjin Zhao
Dry eye disease (DED) is characterized by chronic inflammation and an unstable tear film. Stem cells have shown potential for DED treatment, but the main challenge lies in improving cell delivery effectiveness. Here, we developed eye drops for autoimmune DED treatment using porous arginine–glycine–aspartic acid (RGD)–modified alginate microcarriers with mesenchymal stem/stromal cells (MSCs) (RGD-Alg@MSCs). These microcarriers provided a favorable microenvironment for large-scale cell expansion while maintaining stemness with ideal mechanical properties for ocular application. In vitro, RGD-Alg@MSCs demonstrated significantly enhanced therapeutic effects compared to conventional MSCs, including improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced release of immunomodulatory factors. Transcriptomic analysis revealed distinct molecular mechanisms underlying these enhanced therapeutic effects. In the mouse model, RGD-Alg@MSCs exhibited prolonged ocular retention and enhanced tear production, promoted corneal healing, and suppressed inflammation by inhibiting dendritic cell activation and T H 17 differentiation. Our microcarrier system substantially improves stem cell delivery efficiency for treating autoimmune DED.
研究领域:
眼科
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免疫学
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再生医学
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药物递送
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分子生物学
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转化医学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2016
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IF 0.62
Jian Sun,Tao Liu,Jianhua Xu
Alfa-hederin (Hed) is regarded as a promising drug in cancer therapy especially in drug-resistant cancers. However, its reduced anticancer activity caused by protein absorption limits its wide clinical applications. The purpose of this study was to develop diblock copolymer-based micelles as an integrated platform for targeted delivery of Hed to overcome its intrinsic drawbacks. Amphiphilic diblock copolymers, poly(epsilon-caprolactone)- b -poly(oligo(ethylene glycol) monomethyl ether methacrylate- co -RGD) (PCL- b -P(OEGMA- co -RGD)) consisting of hydrophobic PCL, hydrophilic POEGMA and targeting peptide (RGD) were fabricated via the combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and polymer post-functionalization. Hed-containing targeting micellar nanoparticles , Hed-NP-RGD, were obtained via the co-micellization of PCL- b -P(OEGMA- co -RGD) and Hed, showing hydrodynamic diameter 108 ± 1 nm and zeta potential −4.10 ± 0.15 mV. In vitro experiments demonstrated that Hed-NP-RGD possessed superior anti-proliferative and cellular apoptosis in comparison with that of free Hed possibly due to the assumption that the presence of polymeric micelles protected Hed molecules from absorption by proteins and tumor-targeting effect.
研究领域:
药学
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聚合物化学
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癌症研究
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纳米技术
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DOI
高影响因子
TALANTA
·
2018
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IF 4.244
Kai Dong,Yan Zhang,Lu Zhang,Zhenzhen Wang,Jinsong Ren,Xiaogang Qu
Nowadays, cancer has been one of the major threats to human beings throughout the world. Nanomedicines have been demonstrated as a promising candidate for cancer chemotherapy. In this work, we facilely constructed a RGD (Arg-Gly-Asp) modified [email protected] imidazolate framework-8 ( [email protected] @ZIF-8) as a novel metal-organic frameworks-based hydrophobic drug delivery system for targeted and enhanced cancer treatment. In our system, the nanoplatform exhibited the superior property of target to the cancer cells due to the function with RGD. More importantly, the [email protected] @ZIF-8 nanoplatform has shown the enhanced cancer cell treatment due to the excellent pH-responsive hydrophobic anticancer drug delivery and intracellular ROS generation. With the excellent targeting and enhanced therapy performance, we envision that the hydrophobic anticancer drug delivery system could become a potential therapeutic agent for targeted cancer treatment.
研究领域:
肿瘤学
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药剂学
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纳米生物技术
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
·
IF 5.268
Shuang Fu,Yinan Zhao,Jiao Sun,Ting Yang,Defu Zhi,Enxia Zhang,Fangli Zhong,Yuhong Zhen,Shufen Zhang,Shubiao Zhang
Conventional chemotherapy for tumor treatment remains flawed because it fails to limit cytotoxicity to a small set of selectable tissues. Active targeting techniques for the delivery of drugs to specific sites are increasingly used to enhance drug accumulation at tumor sites with the aim of reducing side effects in vivo . Liposomes, modified with different targeting ligands, are considered to be one of the most promising targeted drug carriers. Herein, novel linear and cyclic arginine-glycine-aspartate (RGD) peptide-based lipids were synthesized to develop modified liposomal drug delivery systems with active targeting and pH-sensitivity. The RGD-modified liposomes showed excellent active targeting ability for integrin α v β 3 receptors, resulting in improved cellular uptake. The modified liposomes also enhanced intracellular doxorubicin (DOX) release because of their degradation in an acidic environment. Consequently, the RGD-modified, DOX-loaded liposomes exhibited significant antitumor efficacy and low toxicity in vitro and in vivo . In particular, 5% cRGD-lipid modified DOX-loaded liposome showed the greatest inhibition of tumor growth in mice among the tested formulations, and much less toxicity than free DOX. In conclusion, the DOX-loaded pH-sensitive liposome modified with 5% cRGD-lipid developed in the current study provides a potential approach for improved tumor therapy.
研究领域:
药学
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癌症研究
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药物递送系统
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Zhengjie Zhou,Yang Yan,Li Wang,Qiang Zhang,Yiyun Cheng
Photothermal therapy efficiently ablates tumors via hyperthermia but inevitably induces serious side effects including thermal damage to normal tissues, inflammations and enhanced risk of tumor metastasis. In this study, we fabricated a dual peptide decorated melanin-like nanoparticle for tumor-targeted and autophagy-promoted photothermal therapy in pursuit of improved cancer treatment. The multifunctional nanoparticle was composed of dual peptide RGD- and beclin 1-modified and PEGylated melanin-like polydopamine nanoparticles. Beclin 1-derived peptide modified on the nanoparticle up-regulated autophagy in cancer cells and further sensitized the tumors to photothermal ablation. RGD decorated on the particle surface enhanced the selectivity and cellular uptake of polydopamine nanoparticles by breast cancer cells. In vivo therapeutic experiments revealed that the tumor-targeted and autophagy promotion-associated photothermal therapy efficiently regressed tumors at a low temperature around 43 °C. The study provides a novel and efficient strategy to improve the efficiency of photothermal therapy via the up-regulation of autophagy in tumor cells.
研究领域:
纳米技术
·
癌症治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Pengpeng Guan,Caijie Yuan,Jiali Li,Kun Yu,Ruiqi Xie,Enling Hu,Weiwei Ding,Guangqian Lan,Fei Lu
In the treatment of thrombosis, conventional nanocarriers inevitably have problems, such as adverse reactions and difficulties in synthesis. Inspired by the concept of ‘medicine food homology,’ we extracted and purified natural exosomes from mulberry leaves as carriers for the delivery of urokinase-type plasminogen activator (uPA) for targeted therapy. The obtained mulberry leaf exosomes (MLE) possessed a desirable hydrodynamic particle size (119.4 nm), a uniform size distribution (polydispersity index = 0.174), and a negative surface charge (−23.3 mv). Before loading with uPA, MLE were grafted with cyclic RGD (cRGD) to selectively bind activated platelets for thrombus targeting. The cytometry studies revealed that MLE@cRGD has a high thrombus targeting ability about 74.3 %. Animal tests demonstrated that the delivered uPA could dissolve clots almost completely in femoral vein thrombosis models. In addition, MLE could remodel venous microenvironments by effectively eliminating reactive oxygen species (ROS) and promoting the phenotypic transformation of macrophages from M1 to M2 for venous tissue repair.
研究领域:
药理学
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纳米技术
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治疗学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2019
·
IF 13.903
Jun Dai,Yinghao Li,Zi Long,Ruming Jiang,Zeyan Zhuang,Zhiming Wang,Zujin Zhao,Xiaoding Lou,Fan Xia,Ben Zhong Tang
Photodynamic therapy (PDT) strategy has been widely used in tumor treatment, and the reagents for reactive oxygen species (ROS) play a crucial role. Herein, we develop a fluorogen (TTB) containing an electron-accepting benzo[1,2-b:4,5-b′]dithiophene 1,1,5,5-tetraoxide core and electron-donating 4,4′-(2,2-diphenylethene-1,1-diyl)bis(N,N-diphenylaniline) groups for image-guided targeting PDT application. TTB exhibits a prominent aggregation-induced emission (AIE) property with strong near-infrared (NIR) fluorescence in aggregates and is capable of efficiently generating ROS of O2•– and 1O2 under white light irradiation. The nanoparticles (RGD-4R-MPD/TTB NPs) with NIR emission (∼730 nm), high photostability, and low dark cytotoxicity are fabricated by encapsulating TTB within polymeric matrix and then modified with RGD-4R peptide. They show excellent performance in targeting PDT treatment of PC3, HeLa, and SKOV-3 cancer cells in vitro. The investigations on pharmacokinetics, biodistribution, and long-term tracing in vivo reveal that RGD-4R-MPD/TTB NPs can selectively accumulate in tumors for real-time, long-term image-guided PDT treatment. The RGD-4R-MPD/TTB NPs-mediated PDT in multiple xenograft tumor models disclose that the growth of cervical, prostate, and ovarian cancers in mice can be effectively inhibited. These results demonstrate that the reagents employing NIR fluorogen TTB as a photosensitizer could be promising candidates for in vivo image-guided PDT treatments of tumors.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Suhua Jiang,Fukai Zhu,Yang Lin,Liu Ran,Fulin Lin,Haina Tian,Ting Hu,Peiyuan Wang,Canzhong Lu
Owing to residual tumor tissues around the treatment margins, it is difficult to totally ablate large tumors, eliminate disseminated and metastatic nodules as well as prevent the tumor recurrence simultaneously by conventional photothermal therapy (PTT). In this work, PTT combined reactive oxygen species oxidative therapy (ROT) was conducted via mesoporous polydopamine nanosphere with nanoceria doping (MPDA-Ce). After surface anchoring with Arg-Gly-Asp (RGD) molecules, the dispersive stability and tumor targeting of this innovative nanoplatform were substantially boosted. In vitro studies revealed that the unique nanotherapeutics had satisfactory photothermal conversion efficiency (η = 51.41%), continuous nanoceria release in cytoplasm of tumor cells after acid microenvironment (pH = 5.5) induced biodegradation. Significantly, hyperthermia amplified the abundant reactive oxygen species generation under 808 nm laser irradiation that potent ROT was realized with only 27.1% cells alive. Strikingly, Indocyanine green (ICG) loaded MPDA-Ce with RGD modification shows robust tumor targeting capability in breast carcinoma bearing Balb/C mice under fluorescent imaging in the second near-infrared window. The combined treatments resulted in complete tumor cells eradication under 808 nm laser illumination both in vitro and in vivo . This work highlights the promising application of MPDA-Ce as a powerful nanoplatform for ROT and PTT combined treatment in clinical.
研究领域:
癌症治疗
·
纳米医学
·
材料科学
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产品关联
DOI
高影响因子
Advanced Therapeutics
·
2023
·
IF 4.6
XiaoJie Song,Kang-Li Lan,Yi-Fei Xue,Hong-Min Liu,Qi-Yan Lv,Zhen Zhao,Hui-Fang Cui
Camptothecin (CPT) is impeded by low solubility, non-tumor-targeting ability, and fast blood clearance. Self-assembly of hydrophobic drugs into nanostructures, especially nanoparticles (NPs), can improve their anti-cancer effects. In this study, arginine-glycine-aspartic acid (RGD), a hydrophilic and tumor-targeting peptide, is conjugated with CPT through a glutathione-cleavable disulfide bond. The synthesized amphiphilic molecule CPT-ss-RGD self-assembled into stable NPs in an aqueous solution with diameters of ≈86nm. They exhibited low critical aggregation concentrations, good stability, and glutathione responsiveness. They can be specifically taken up by CRC cells through RGD integrin-mediated uptake, and exhibit high toxicity to CRC cells and multicellular tumor spheroids. As expected, CPT-ss-RGD NPs prolonged the blood circulation time and enhanced the tumor accumulation of CPT, exhibiting excellent anti-tumor growth ability and few side effects. Thus, CPT-ss-RGD NPs have great clinical translational potential for CRC therapy. The successful self-assembly of the CPT-ss-RGD NPs provides a new method for the self-delivery of hydrophobic therapeutics in vivo.
研究领域:
药学
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纳米技术
·
肿瘤学
·
药物递送系统
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产品关联
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Congyi Shen,Jian Wang,Guangfeng Li,Shuyue Hao,Yan Wu,Peiran Song,Yafei Han,Mengmeng Li,Guangchao Wang,Ke Xu,Hao Zhang,Xiaoxiang Ren,Yingying Jing,Ru Yang,Zhen Geng,Jiacan Su
Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.
研究领域:
生物医学工程
·
再生医学
·
组织工程
·
干细胞生物学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Feihu Wang,Qian Huang,Yun Wang,Wenjun Zhang,Ran Lin,Yanna Yu,Yuanyuan Shen,Honggang Cui,Shengrong Guo
Simultaneous inhibition of both tumor growth and metastasis is the key to treating metastatic cancer, yet the development of effective drug delivery systems represents a great challenge since multimodal therapeutic agents must be rationally combined to overcome the biological mechanisms underpinning tumor cell proliferation and invasion. In this context, we report a hybrid therapeutic nanoscale platform that incorporates an anti-proliferative drug, doxorubicin (DOX), and an anti-NF-κB agent, p65-shRNA, for effective treatment of metastatic breast cancer. In our design, we first conjugated DOX via an acid-labile linker onto gold nanorods that were pre-modified with the tumor targeting peptide RGD and a positively charged, disulfide cross-linked short polyethylenimines (DSPEI), and then incorporated shRNA through electrostatic complexation with DSPEI. We show that this “all in one” nanotherapeutic system (RDG/shRNA@DOX) can be effectively internalized through RGD-mediated endocytosis , followed by stimuli-responsive intracellular co-release of DOX and shRNA. Our in vitro experiments suggest that this multimodal system can significantly inhibit cell proliferation, angiogenesis , and invasion of metastatic MDA-MB-435 cancer cells. Systemic administration of RDG/shRNA@DOX into a metastatic mouse model led to enhanced tumor accumulation, and, most importantly, significant inhibition of in situ tumor growth and almost complete suppression of tumor metastasis. We believe this hybrid multimodal nanotherapeutic system provides important insight into the rational design of therapeutic systems for the effective treatment of metastatic carcinoma. Statement of Significance The key to successfully treat metastatic cancer is the simultaneous inhibition of both tumor growth and metastasis. This represents a great challenge for the design of drug delivery systems since multimodal therapeutic agents must be rationally combined to overcome the respective biological mechanisms underpinning tumor cell proliferation and invasion. Toward this end, we developed a hybrid nanomedicine platform that incorporates an anti-proliferative drug, doxorubicin (DOX), and an anti-NF-κB agent, p65-shRNA, for effective treatment of metastatic breast cancer. We showed that this multimodal system (RDG/shRNA@DOX) enhanced tumor accumulation, led to prolonged circulation, and most importantly, significant inhibition of in situ tumor growth and almost complete suppression of tumor metastasis. We believe this hybrid multimodal nanotherapeutic system provides significant insight into the rational design of therapeutic systems for the effective treatment of metastatic cancer.
研究领域:
纳米医学
·
肿瘤学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子